The proposed research will continue our investigation of the key sensory and pharmacologic components of cigarette smoke. These studies will elucidate the importance of each component as well as their interaction in the maintenance of tobacco dependence. Using procedures developed in the previous period of grant support, we can selectively provide the sensory qualities of cigarette smoke with very little nicotine by means of an aerosol containing a small quantity of smoke constituents. Conversely, we can selectively provide a pharmacologically effective dose of nicotine without other smoke constituents and without the usual sensory cues of smoke, by means of an aerosol containing nicotine microencapsulated in liposomes (phospholipid bilayers). We will use these aerosols to determine the relative importance of sensory and pharmacologic stimulation in assisting smokers to abstain from cigarette smoking during an all-day experimental session. We will also determine the efficacy of these aerosols in relieving craving for cigarettes and other smoking withdrawal symptoms when cigarette abstinence is enforced throughout the day. Preference for the sensory cues of smoke vs the systemic pharmacologic effects of nicotine will be assessed using a forced-choice procedure. To examine mechanisms that may underly relapse, the possible enhancement of craving by exposure to smoke-related cues (priming effect) will be measured. To study the process by which sensory cues are established as conditioned reinforcers, we will assess the ability of nicotine to reinforce preference for a new taste cue with which it is paired. The results of these studies will increase our understanding of learned associations underlying tobacco dependence, and the relative role of sensory cues and pharmacologic effects of nicotine in maintaining smoking behavior. Moreover, the results will provide useful information about the potential efficacy of two aerosol techniques in smoking cessation treatment.